Treatment of Amiodarone-Induced Thyrotoxicosis Type 2: A Randomized Clinical Trial

Silvia A. Eskes; Erik Endert; Eric Fliers; Ronald B. Geskus; Robin P. F. Dullaart; Thera P. Links; Wilmar M. Wiersinga

doi:10.1210/jc.2011-2390

Treatment of Amiodarone-Induced Thyrotoxicosis Type 2: A Randomized Clinical Trial

Silvia A. Eskes^*, Erik Endert, Eric Fliers, Ronald B. Geskus, Robin P. F. Dullaart, Thera P. Links, Wilmar M. Wiersinga

^*Corresponding author for this work

Faculty of Medical Sciences/UMCG

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Context: Amiodarone-induced thyrotoxicosis (AIT) type 2 is self-limiting in nature, but most physicians are reluctant to continue amiodarone. When prednisone fails to restore euthyroidism, possibly due to mixed cases of AIT type 1 and 2, perchlorate (ClO4) might be useful because ClO4 reduces the cytotoxic effect of amiodarone on thyrocytes.

Objectives: Our objectives were to demonstrate the feasibility of continuation of amiodarone in AIT type 2 and to evaluate the usefulness of ClO4 (given alone or in combination with prednisone) in AIT type 2.

Design and Setting: A randomized multicenter study was conducted in 10 Dutch hospitals.

Methods: Patients with AIT type 2 were randomized to receive prednisone 30 mg/d (group A, n = 12), sodium perchlorate 500 mg twice daily (group B, n = 14), or prednisone plus perchlorate (group C, n = 10); all patients continued amiodarone and were also treated with methimazole 30 mg/d. Follow-up was 2 yr.

Main Outcome Measures: Treatment efficacy (defined as TSH values >= 0.4 mU/liter under continuation of amiodarone) and recurrent thyrotoxicosis were evaluated.

Results: Initial therapy was efficacious in 100, 71, and 100% of groups A, B, and C, respectively (P = 0.03). The 29% failures in group B became euthyroid after addition of prednisone. Neither the time to reach TSH of 0.4 mU/liter or higher [8 wk (4-20), 14 wk (4-32), and 12 wk (4-28) in groups A, B, and C respectively] nor the time to reach free T-4 of 25 pmol/liter or below [4 wk (4-20), 12 wk (4-20), and 8 wk (4-20) in groups A, B, and C) were significantly different between groups (values as median with range). Recurrent thyrotoxicosis occurred in 8.3%.

Conclusion: Euthyroidism was reached despite continuation of amiodarone in all patients. Prednisone remains the preferred treatment modality of AIT type 2, because perchlorate given alone or in combination with prednisone had no better outcomes. (J Clin Endocrinol Metab 97:499-506, 2012)

Original language	English
Pages (from-to)	499-506
Number of pages	8
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	97
Issue number	2
DOIs	https://doi.org/10.1210/jc.2011-2390
Publication status	Published - Feb-2012

Keywords

IN-VITRO
CONTINUATION
THYROIDITIS
PERCHLORATE
MANAGEMENT

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@article{a693cf7e3e0f401da5345fe97208f9c6,

title = "Treatment of Amiodarone-Induced Thyrotoxicosis Type 2: A Randomized Clinical Trial",

abstract = "Context: Amiodarone-induced thyrotoxicosis (AIT) type 2 is self-limiting in nature, but most physicians are reluctant to continue amiodarone. When prednisone fails to restore euthyroidism, possibly due to mixed cases of AIT type 1 and 2, perchlorate (ClO4) might be useful because ClO4 reduces the cytotoxic effect of amiodarone on thyrocytes.Objectives: Our objectives were to demonstrate the feasibility of continuation of amiodarone in AIT type 2 and to evaluate the usefulness of ClO4 (given alone or in combination with prednisone) in AIT type 2.Design and Setting: A randomized multicenter study was conducted in 10 Dutch hospitals.Methods: Patients with AIT type 2 were randomized to receive prednisone 30 mg/d (group A, n = 12), sodium perchlorate 500 mg twice daily (group B, n = 14), or prednisone plus perchlorate (group C, n = 10); all patients continued amiodarone and were also treated with methimazole 30 mg/d. Follow-up was 2 yr.Main Outcome Measures: Treatment efficacy (defined as TSH values >= 0.4 mU/liter under continuation of amiodarone) and recurrent thyrotoxicosis were evaluated.Results: Initial therapy was efficacious in 100, 71, and 100% of groups A, B, and C, respectively (P = 0.03). The 29% failures in group B became euthyroid after addition of prednisone. Neither the time to reach TSH of 0.4 mU/liter or higher [8 wk (4-20), 14 wk (4-32), and 12 wk (4-28) in groups A, B, and C respectively] nor the time to reach free T-4 of 25 pmol/liter or below [4 wk (4-20), 12 wk (4-20), and 8 wk (4-20) in groups A, B, and C) were significantly different between groups (values as median with range). Recurrent thyrotoxicosis occurred in 8.3%.Conclusion: Euthyroidism was reached despite continuation of amiodarone in all patients. Prednisone remains the preferred treatment modality of AIT type 2, because perchlorate given alone or in combination with prednisone had no better outcomes. (J Clin Endocrinol Metab 97:499-506, 2012)",

keywords = "IN-VITRO, CONTINUATION, THYROIDITIS, PERCHLORATE, MANAGEMENT",

author = "Eskes, {Silvia A.} and Erik Endert and Eric Fliers and Geskus, {Ronald B.} and Dullaart, {Robin P. F.} and Links, {Thera P.} and Wiersinga, {Wilmar M.}",

year = "2012",

month = feb,

doi = "10.1210/jc.2011-2390",

language = "English",

volume = "97",

pages = "499--506",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

publisher = "Oxford University Press",

number = "2",

}

TY - JOUR

T1 - Treatment of Amiodarone-Induced Thyrotoxicosis Type 2

T2 - A Randomized Clinical Trial

AU - Eskes, Silvia A.

AU - Endert, Erik

AU - Fliers, Eric

AU - Geskus, Ronald B.

AU - Dullaart, Robin P. F.

AU - Links, Thera P.

AU - Wiersinga, Wilmar M.

PY - 2012/2

Y1 - 2012/2

N2 - Context: Amiodarone-induced thyrotoxicosis (AIT) type 2 is self-limiting in nature, but most physicians are reluctant to continue amiodarone. When prednisone fails to restore euthyroidism, possibly due to mixed cases of AIT type 1 and 2, perchlorate (ClO4) might be useful because ClO4 reduces the cytotoxic effect of amiodarone on thyrocytes.Objectives: Our objectives were to demonstrate the feasibility of continuation of amiodarone in AIT type 2 and to evaluate the usefulness of ClO4 (given alone or in combination with prednisone) in AIT type 2.Design and Setting: A randomized multicenter study was conducted in 10 Dutch hospitals.Methods: Patients with AIT type 2 were randomized to receive prednisone 30 mg/d (group A, n = 12), sodium perchlorate 500 mg twice daily (group B, n = 14), or prednisone plus perchlorate (group C, n = 10); all patients continued amiodarone and were also treated with methimazole 30 mg/d. Follow-up was 2 yr.Main Outcome Measures: Treatment efficacy (defined as TSH values >= 0.4 mU/liter under continuation of amiodarone) and recurrent thyrotoxicosis were evaluated.Results: Initial therapy was efficacious in 100, 71, and 100% of groups A, B, and C, respectively (P = 0.03). The 29% failures in group B became euthyroid after addition of prednisone. Neither the time to reach TSH of 0.4 mU/liter or higher [8 wk (4-20), 14 wk (4-32), and 12 wk (4-28) in groups A, B, and C respectively] nor the time to reach free T-4 of 25 pmol/liter or below [4 wk (4-20), 12 wk (4-20), and 8 wk (4-20) in groups A, B, and C) were significantly different between groups (values as median with range). Recurrent thyrotoxicosis occurred in 8.3%.Conclusion: Euthyroidism was reached despite continuation of amiodarone in all patients. Prednisone remains the preferred treatment modality of AIT type 2, because perchlorate given alone or in combination with prednisone had no better outcomes. (J Clin Endocrinol Metab 97:499-506, 2012)

AB - Context: Amiodarone-induced thyrotoxicosis (AIT) type 2 is self-limiting in nature, but most physicians are reluctant to continue amiodarone. When prednisone fails to restore euthyroidism, possibly due to mixed cases of AIT type 1 and 2, perchlorate (ClO4) might be useful because ClO4 reduces the cytotoxic effect of amiodarone on thyrocytes.Objectives: Our objectives were to demonstrate the feasibility of continuation of amiodarone in AIT type 2 and to evaluate the usefulness of ClO4 (given alone or in combination with prednisone) in AIT type 2.Design and Setting: A randomized multicenter study was conducted in 10 Dutch hospitals.Methods: Patients with AIT type 2 were randomized to receive prednisone 30 mg/d (group A, n = 12), sodium perchlorate 500 mg twice daily (group B, n = 14), or prednisone plus perchlorate (group C, n = 10); all patients continued amiodarone and were also treated with methimazole 30 mg/d. Follow-up was 2 yr.Main Outcome Measures: Treatment efficacy (defined as TSH values >= 0.4 mU/liter under continuation of amiodarone) and recurrent thyrotoxicosis were evaluated.Results: Initial therapy was efficacious in 100, 71, and 100% of groups A, B, and C, respectively (P = 0.03). The 29% failures in group B became euthyroid after addition of prednisone. Neither the time to reach TSH of 0.4 mU/liter or higher [8 wk (4-20), 14 wk (4-32), and 12 wk (4-28) in groups A, B, and C respectively] nor the time to reach free T-4 of 25 pmol/liter or below [4 wk (4-20), 12 wk (4-20), and 8 wk (4-20) in groups A, B, and C) were significantly different between groups (values as median with range). Recurrent thyrotoxicosis occurred in 8.3%.Conclusion: Euthyroidism was reached despite continuation of amiodarone in all patients. Prednisone remains the preferred treatment modality of AIT type 2, because perchlorate given alone or in combination with prednisone had no better outcomes. (J Clin Endocrinol Metab 97:499-506, 2012)

KW - IN-VITRO

KW - CONTINUATION

KW - THYROIDITIS

KW - PERCHLORATE

KW - MANAGEMENT

U2 - 10.1210/jc.2011-2390

DO - 10.1210/jc.2011-2390

M3 - Article

SN - 0021-972X

VL - 97

SP - 499

EP - 506

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 2

ER -

Treatment of Amiodarone-Induced Thyrotoxicosis Type 2: A Randomized Clinical Trial

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